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Biomedical subjects

R V Heatley

Publications and source records attributed to R V Heatley.

At least 73 records · Page 4Linked to original sources
PubMed1989

Colonic mucosal T lymphocytes in ulcerative colitis: expression of CD7 antigen in relation to MHC class II (HLA-D) antigens.

T-cell subsets and their activation state were examined by double-label immunofluorescence of cryostat tissue sections of the colon from 21 patients with ulcerative colitis (UC) and 30 histologically normal controls. Expression of MHC class I (HLA-A, B, C) and class II (HLA-D) antigens was studied in parallel. In the normal colonic mucosa, the CD4:CD8 ratio in the epithelial compartment approximated 1:1, and in the lamina propria, 2.55:1. Of the CD8+ (cytotoxic/suppressor) subset, approximately half did not express the CD5 "pan-T" marker in either compartment. Virtually no Leu8+ cells were observed, implying that the CD4+ subset consisted of helper, rather than suppressor-inducer cells. Classical markers of T-cell activation (CD25, HLA-D) and proliferation were absent, and strong expression of the CD7 "immunostimulation" marker was approximately equal in both CD4 and CD8 subsets. The epithelium was uniformly negative for class II antigens, but positive for class I. In UC, there were no significant alterations in CD4:CD8 ratios in either compartment, and there were no changes with respect to phenotype of the subsets. In 11 of 19 patients (mainly with total colitis), enterocytes were HLA-D+. In this HLA-D+ group, there was an increase in the percentage of CD4+ cells coexpressing CD7; this difference was significant (P less than 0.02) in the lamina propria. Increased expression of CD7 was also found by the CD6+ T cell subset (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Ascorbic acid: a factor concentrated in human gastric juice.

1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A + D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology. 2. A significant reduction in gastric juice ascorbic acid (A + D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis. 3. Concentrations of ascorbic acid (A + D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach. 4. These data demonstrate that considerable quantities of ascorbic acid (A + D) are normally 'secreted' into the stomach. 5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form.

Adult↗
PubMed1989

Glycoprotein synthesis and secretion by cultured small intestinal mucosa in coeliac disease.

Glycoprotein biosynthesis by jejunal mucosa was examined during culture in vitro in 26 patients with coeliac disease and 19 controls. The incorporation rates of tritiated glucosamine into tissue and secreted glycoproteins were determined using established techniques. The total glucosamine incorporation in untreated coeliac patients was significantly greater than that of histologically normal mucosa (p less than 0.001) and jejunal tissue from patients with treated coeliac disease (p less than 0.01). Enhanced secretion of in vitro labelled glycoproteins was observed in untreated coeliac patients. The total incorporation of tritiated glucosamine in intestinal tissues was correlated with goblet cell numbers. These results indicate that quantitative changes in glycoprotein synthesis and secretion occur in coeliac disease.

Adolescent↗
PubMed1989

Immunoglobulin secretion by isolated intestinal lymphocytes: spontaneous production and T-cell regulation in normal small intestine and in patients with coeliac disease.

The in vitro secretion of immunoglobulins by small intestinal lymphocytes isolated from 47 patients with normal histology and 23 patients with treated and untreated coeliac disease was examined using an enzyme linked immunosorbent assay. In control patients, duodenal lymphocytes spontaneously secreted higher levels of IgM than jejunal lymphocytes (p less than 0.05). Significantly higher levels of both IgA (p less than 0.05) and IgM (p less than 0.001) were secreted by jejunal lymphocytes of 10 patients with untreated coeliac disease than cells isolated from normal jejunal tissue. IgM and IgA secretion by duodenal lymphocytes isolated from control patients was increased in a dose dependent manner by coculture with autologous peripheral blood T lymphocytes. This effect was not observed with jejunal lymphocytes of control or treated coeliac patients. Peripheral T-cells of untreated coeliac patients, however, showed significant helper effects (p less than 0.05) for IgM and IgA secretion by autologous jejunal lymphocytes. The results suggest that jejunal lymphocytes of patients with untreated coeliac disease show major differences in their capacity to synthesise and secrete immunoglobulins in vitro and the enhanced secretion might result from changes in T-cell immunoregulatory function.

Adolescent↗
PubMed1989

Expression of CD6 and the UCHL1-defined CD45 (p180) antigen by human colonic T lymphocytes.

Cryostat sections of histologically normal human colon were studied by double-label immunofluorescence techniques using a panel of monoclonal antibodies to T-lineage antigens and activation markers, with particular reference to the CD6 antigen. In the lamina propria, the majority population of T cells was of the CD3+, CD6+, CD4+ subset, of which virtually all were of the UCHL1+, CD45R-, Leu 8- phenotype of antigen-committed helper T cells. This majority lamina propria population did not express markers associated with blastogenesis (CD7), activation (MHC class II, CD25, CD38) or proliferation (OKT9, Ki67). In both intra-epithelial and lamina propria compartments, a subpopulation of CD3+ T cells was identified which did not express either the CD6 or CD5 peripheral 'pan T' markers. Most of the CD3+, CD6- cells were of the CD8+ (cytotoxic-suppressor) subset which co-expressed the CD7 antigen with a much higher frequency than did the CD6+ subpopulation. Expression of CD25, CD38 and HLA-D antigens, although infrequent, was confined to this CD8+, CD5-, CD6- population. Our data thus imply that the colonic mucosa is largely populated by mature, antigen-committed resting T cells of the helper-inducer phenotype.

Antigens, CD↗
PubMed1989

Serum interleukin-2-receptor in coeliac disease: response to treatment and gluten challenge.

Concentrations of the soluble interleukin-2 receptor (sIL-2R) in the serum of 33 patients with coeliac disease were measured by ELISA. The levels of sIL-2R were significantly raised in 15 patients with untreated coeliac disease compared with treated patients and age- and sex-matched symptomatic and non-symptomatic control groups. Longitudinal studies in individual coeliac patients showed that serum sIL-2R fell following commencement of a gluten-free diet. Gluten challenge of 16 treated coeliac patients for 1 week resulted in a significant increase in serum sIL-2R, which returned to prechallenge levels within 4 weeks of recommencement of a gluten-free diet. We suggest that serum sIL-2R levels in patients with coeliac disease reflect specific immunological activation in response to gluten ingestion. Measurement of serum sIL-2R may therefore be useful in the assessment of response to treatment in patients with coeliac disease.

Adolescent↗
PubMed1988

In vitro mucus glycoprotein production by colonic tissue from patients with ulcerative colitis.

Colonic mucus production was measured in vitro by means of incorporation of tritiated glucosamine using biopsy material from patients with ulcerative colitis and compared with data from patients with Crohn's disease, colonic carcinoma, colonic polyps and patients with apparently normal colonic mucosae. Mucus production was significantly decreased (p less than 0.03) in all patients with ulcerative colitis, and in particular in patients with inactive disease when compared with normal subjects. In patients with active disease mucus production was not significantly different from normal subjects. The radiolabelled material was characterised by gel filtration and ion exchange liquid chromatography as mainly high molecular weight glycoproteins. These results indicate that the quantitative character of colonic mucus is abnormal in inactive ulcerative colitis.

Colitis, Ulcerative↗
PubMed1988

Local immunity in ulcerative colitis: evidence for defective secretory IgA production.

To investigate local humoral immunity in ulcerative colitis (UC), immunoglobulin (Ig) contents and net Ig production in vitro was assessed using organ cultures of colonic biopsies from 21 patients with quiescent disease and 11 controls. Ig was estimated by enzyme linked immunoassay (ELISA) for IgA, secretory IgA (sIgA), IgM, and IgG. In parallel, numbers of IgA plasma cells were estimated by indirect immunoperoxidase staining of tissue sections for IgA. IgA was the dominant Ig isotype found pre-existing in colonic mucosae, and secreted in vitro. In UC patients, preformed tissue IgA and IgA produced in vitro were significantly increased compared with controls. There was no concomitant increase in amounts of sIgA synthesised in culture, however, although numbers of IgA plasma cells were increased in UC patients by an amount comparable with the increased in vitro IgA production. These results directly show a dysfunction of transepithelial IgA secretion in quiescent ulcerative colitis. Despite a significantly raised concentration of tissue IgG in UC patients, little was produced in vitro in patient and control groups alike, suggesting that mucosal IgG was serum derived, and not linked to local IgA production.

Adult↗
PubMed1988

T lymphocytes of the human colonic mucosa: functional and phenotypic analysis.

Normal human colonic lymphocyte populations were isolated for both phenotypic analysis by double-label immunofluorescence and assessment for regulatory effects on Ig production by co-culture with responder cells from colonic mucosa and peripheral blood. Mean CD4:CD8 ratios for colonic intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL) were comparable to values obtained from tissue sections. IEL alone did not produce Ig in vitro and were without effect on Ig production when co-cultured with LPL. However, T-enriched LPL had a marked helper effect for T-depleted LPL. Maximal help was for IgA production, increasing with numbers of T-enriched cells. In colonic LPL T-depleted and T-enriched co-cultures, pokeweed mitogen (PWM) had no significant effect. By contrast, in co-cultures of T-enriched and T-depleted peripheral blood mononuclear cells, Ig production was PWM-dependent. In all experiments with colonic mucosal responder cells, IgG production was low. The effects of unfractionated colonic biopsy lymphocytes on T-depleted peripheral blood mononuclear cells were additive for IgM production and synergistic for IgA synthesis, although almost no IgG was produced. Moreover, PWM had helper effects for IgM, but was suppressive for IgA production. These data suggest that colonic mucosal regulatory cells reside in the lamina propria, and predominantly provide help for IgA and IgM synthesis. The data further suggest the existence of a pre-stimulated IgA-specific T helper cell population.

Antigens, Surface↗
PubMed1988

Possible pathogenetic pathways of Campylobacter pylori in gastro-duodenal disease.

The exact pathogenic mechanisms involved in Campylobacter pylori associated gastro-duodenal inflammation are unclear. C. pylori adheres to gastric type epithelium and colonisation is associated with a number of ultrastructural abnormalities. Other factors thought important include the marked bacterial urease activity, enzymatic degradation of the mucous layer and possible toxins. The induced inflammatory reaction will also contribute to tissue damage and a breakdown of normal defense mechanisms.

Antibody Formation↗